Anxiety and depressive symptoms and migraine-related outcomes in children and adolescents.

OBJECTIVE: The objective of this study was to explore the longitudinal relationship between anxiety and depressive symptoms and migraine outcomes in children and adolescents. BACKGROUND: Children and adolescents with migraine experience more anxiety and depressive symptoms than their peers without migraine, but it is unknown if these symptoms are associated with differential migraine outcomes. METHODS: In this prospective clinical cohort study, children and adolescents aged 8.0-18.0 years with migraine completed headache questionnaires and validated measures of anxiety and depressive symptoms (Patient-Reported Outcomes Measurement Information System) at an initial consultation and at their first follow-up visit with a neurologist. Changes in monthly headache frequency and changes in migraine-related disability (Pediatric Migraine Disability Assessment) were tracked at each time point. The relationships between these migraine outcomes and anxiety and depressive symptoms were estimated using models controlling for sex, age, headache frequency, and treatment type. RESULTS: There were 123 consenting participants. In models adjusted for age, sex, baseline disability score, and treatment type, baseline anxiety and depressive symptom levels were not significantly associated with change in headache frequency (for anxiety symptoms: ß = -0.05, 95% confidence interval [CI] = -0.268 to 0.166, p = 0.639; for depressive symptoms: ß = 0.14, 95% CI = -0.079 to 0.359, p = 0.209). Similarly, in models adjusted for age, sex, baseline headache frequency, and treatment type, the change in disability was not associated with baseline anxiety (ß = -0.45, 95% CI = -1.69 to 0.78, p = 0.470), nor with baseline depressive symptom scores (ß = 0.16, 95% CI = -1.07 to 1.40, p = 0.796). In post hoc exploratory analyses (N = 84 with anxiety and N = 82 with depressive symptom data at both visits), there were also no significant associations between change in mental health symptoms and change in headache frequency (for anxiety symptoms: ß = -0.084, 95% CI = -0.246 to 0.078, p = 0.306; for depressive symptoms: ß = -0.013, 95% CI = -0.164 to 0.138, p = 0.865). Similarly, the change in disability scores between visits was not related to the change in anxiety (ß = 0.85, 95% CI = -0.095 to 1.78, p = 0.077) nor depressive symptom scores (ß = 0.32, 95% CI = -0.51 to 1.15, p = 0.446). CONCLUSION: Baseline anxiety and depressive symptom levels were not associated with longitudinal migraine outcomes and neither were longitudinal changes in anxiety and depressive symptom levels; this contradicts popular clinical belief that mental health symptoms predict or consistently change in tandem with migraine outcomes.

The waiting game: investigating the neurobiological transition from acute to persistent pain in adolescent rats.

Persistent postsurgical pain affects 20% of youth undergoing a surgical procedure, with females exhibiting increased prevalence of chronic pain compared with males. This study sought to examine the sexually-dimorphic neurobiological changes underlying the transition from acute to persistent pain following surgery in adolescence. Male and female Sprague Dawley rats were randomly allocated to a sham or injury (plantar-incision surgery) condition and assessed for pain sensitivity while also undergoing magnetic resonance imaging at both an acute and chronic timepoint within adolescence. We found that injury resulted in persistent pain in both sexes, with females displaying most significant sensitivity. Injury resulted in significant gray matter density increases in brain areas including the cerebellum, caudate putamen/insula, and amygdala and decreases in the hippocampus, hypothalamus, nucleus accumbens, and lateral septal nucleus. Gray matter density changes in the hippocampus and lateral septal nucleus were driven by male rats whereas changes in the amygdala and caudate putamen/insula were driven by female rats. Overall, our results indicate persistent behavioral and neurobiological changes following surgery in adolescence, with sexually-dimorphic and age-specific outcomes, highlighting the importance of studying both sexes and adolescents, rather than extrapolating from male adult literature.

Photos Sculpt the Stories of Youth: Using Photovoice to Holistically Capture the Lived Experiences and Pain of Youth Who Underwent Spinal Fusion Surgery.

Spinal fusion surgery is one of the most common major surgical procedures in youth. Adolescent idiopathic scoliosis (AIS) is the most frequent reason for corrective spinal fusion. AIS (∼25%-47% of cases) and spinal fusion surgeries are associated with pain, including the development of new onset chronic pain for up to 15% of youth. This research used photovoice approaches to explore the journeys of youth from before, during, and after spinal fusion surgery, to demonstrate their experiences both of and beyond pain. Twenty participants were recruited from a previous study conducted by the senior author's lab. Participants captured photos/videos in their daily life (Phase 1); collected previously taken photos/videos from before/during/after their surgery (Phase 2); and participated in individual interviews to reflexively discuss the meaning behind photos/videos (Phase 3). Before interviews, a questionnaire was administered to assess pain characteristics. Nineteen girls/women with scoliosis and one boy/man with kyphosis (12-19 years old, Mage = 16 years) participated; they identified as white (80%), other (15%), and Southeast Asian (5%). The researchers used a reflexive thematic analysis approach, which generated five themes: (1) body aesthetic versus machine; (2) expectations and anticipation of surgery/outcomes; (3) desire of normalcy and freedom; (4) navigating a hoped-for positive surgery experience; and (5) the journey sculpts identity formation and sense of self. Findings support youth advocacy, underscoring the need to validate youth concerns and inform healthcare professionals of the importance of individualized care. Youth perspectives highlighted opportunities for optimizing surgery/healthcare experiences and the psychosocial impacts of scoliosis on body image and appearance.

Age-related effects on the anterior and posterior hippocampal volumes in 6-21 year olds: A model selection approach.

Although recent studies support significant differences in intrinsic structure, function, and connectivity along the longitudinal axis of the hippocampus, few studies have investigated the normative development of this dimension. In addition, factors known to influence hippocampal structure, such as sex or puberty, have yet to be characterized when assessing age-related effects on its subregions. This study addresses this gap by investigating the relationship of the anterior (antHC) and posterior (postHC) hippocampus volumes with age, and how these are moderated by sex or puberty, in structural magnetic resonance imaging scans from 183 typically developing participants aged 6-21 years. Based on previous literature, we first anticipated that non-linear models would best represent the relationship between age and the antHC and postHC volumes. We found that age-related effects are region-specific, such that the antHC volume remains stable with increasing age, while the postHC shows a cubic function characterized by overall volume increase with age but a slower rate during adolescence. Second, we hypothesized that models, which include biological sex or pubertal status would best describe these relationships. Contrary to expectation, models comprising either biological sex or pubertal status did not significantly improve model performance. Further longitudinal research is needed to evaluate their effects on the antHC and postHC development.

Structural brain network lateralization across childhood and adolescence.

Developmental lateralization of brain function is imperative for behavioral specialization, yet few studies have investigated differences between hemispheres in structural connectivity patterns, especially over the course of development. The present study compares the lateralization of structural connectivity patterns, or topology, across children, adolescents, and young adults. We applied a graph theory approach to quantify key topological metrics in each hemisphere including efficiency of information transfer between regions (global efficiency), clustering of connections between regions (clustering coefficient [CC]), presence of hub-nodes (betweenness centrality [BC]), and connectivity between nodes of high and low complexity (hierarchical complexity [HC]) and investigated changes in these metrics during development. Further, we investigated BC and CC in seven functionally defined networks. Our cross-sectional study consisted of 211 participants between the ages of 6 and 21 years with 93% being right-handed and 51% female. Global efficiency, HC, and CC demonstrated a leftward lateralization, compared to a rightward lateralization of BC. The sensorimotor, default mode, salience, and language networks showed a leftward asymmetry of CC. BC was only lateralized in the salience (right lateralized) and dorsal attention (left lateralized) networks. Only a small number of metrics were associated with age, suggesting that topological organization may stay relatively constant throughout school-age development, despite known underlying changes in white matter properties. Unlike many other imaging biomarkers of brain development, our study suggests topological lateralization is consistent across age, highlighting potential nonlinear mechanisms underlying developmental specialization.

A high-fat high-sugar diet and adversity early in life modulate pain outcomes at the behavioural and molecular level in adolescent rats: The role of sex.

Given that adolescence is a significant period of brain plasticity and development, early life factors have the potential to alter long term outcomes. For instance, adversities such as consumption of a high-fat high-sugar (HFHS) diet and adverse childhood experiences (ACEs; e.g., neglect), and their resulting inflammation and microglial activation can influence pain outcomes by priming the neuroimmune system to overrespond to stressors. Chronic pain is highly prevalent amongst the adolescent population, with the prevalence and manifestation being sexually dimorphic. Although clinical studies show that females are twice as likely to report pain problems compared to males, the majority of pre-clinical work uses male rodents. Therefore, our aim was to examine the effects of sex, a HFHS diet, and an ACE on chronic pain outcomes following a stressor in adolescence. Rat dams were randomly assigned to a Standard or HFHS diet, with pups maintained on their respective diets then randomly allocated to a No Stress or ACE paradigm, and a Sham or Injury condition as a stressor. Results showed that early life adversities increased nociceptive sensitivity, inflammation, and microglial activation systemically and within the brain. Behaviourally, pain outcomes were more prominent in females, however the neuroimmune response was exacerbated in males. These results demonstrate the sexual dimorphism of chronic pain outcomes following early life adversities and provide insight into the mechanisms driving these changes, which will inform more targeted and effective treatment strategies for youth living with chronic pain.

Exploring pain among young people who have completed treatment for acute lymphoblastic leukemia: experiences of youth and caregivers.

PURPOSE: Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed among individuals <14 years of age. The disease and its treatments are associated with negative side effects, including pain, which is both prevalent and distressing. Little is known about pain experiences in this population, which has slowed efforts to identify strategies to mitigate and cope with this adverse effect. This study sought to explore youth's and their caregiver's experiences with, and perspectives of, pain in the context of pediatric cancer treatment. METHODS: Youth and one of their caregivers were recruited through (omitted for peer review). Following completion of a demographic survey, youth and one of their caregivers were interviewed separately using a semi-structured, one-on-one interview guide. Demographic information was analyzed with descriptive statistics, and interviews were transcribed verbatim and analyzed using reflexive thematic analysis. RESULTS: Youth (n = 19; Mage = 15.3 years) and caregiver (n = 19; Mage = 45.4 years) perspectives informed 4 themes: (1) my pain experience is nuanced, multidimensional, and is changing over time; (2) the cancer experience has changed the way I experience and respond to pain; (3) I used strategies to manage pain, and not all of them worked; and (4) my pain experience was influenced by people around me. CONCLUSIONS: Findings extend prior work, suggesting that pain is common, distressing, multidimensional, and influenced by social context. Results highlight the number of ways in which youth and their caregivers attempt to manage their pain and factors influencing pain experiences. Greater efforts are needed to address pain during cancer treatment and survivorship.

Adverse childhood experiences and intimate partner violence: A meta-analysis.

Intimate partner violence (IPV) represents a significant public health concern. Adverse childhood experiences (ACEs) represent one risk factor for IPV, however, the results of existing research on the association between ACEs and IPV demonstrate mixed findings. The present research sought to meta-analytically examine the association between ACEs and (a) IPV perpetration and (b) IPV victimization. Moderator analyses were conducted to determine factors that may impact the association between ACEs and IPV involvement. Electronic searches were conducted in MEDLINE, Embase, and PsycINFO in August of 2021. One-hundred and twenty-three records were screened for inclusion. All studies included a measure of ACEs and IPV victimization or perpetration. Among the 27 studies and 41 samples included in the meta-analysis, 65,330 participants were included. The results of the meta-analyses demonstrated that ACEs were positively associated with IPV perpetration and victimization. Significant methodological and measurement moderators further inform our understanding of ACEs and IPV involvement. The present meta-analyses demonstrates that trauma-informed approaches to IPV screening, prevention, and intervention may be useful, given that individuals who are involved with IPV may be more likely to possess a history of ACEs exposure.

Experiences of medical traumatic stress in parents of children with medical complexity.

BACKGROUND AND OBJECTIVES: Parents of children with medical complexity (CMC) experience high levels of stress and adverse mental health outcomes. Pediatric medical traumatic stress (PMTS) could be an important contributor that has not yet been explored. PMTS describes parents' reactions to their child's illness and medical treatment and can lead to post-traumatic stress symptoms. This is the first study to describe the experiences and impact of PMTS among parents of CMC. METHODS: We conducted semi-structured interviews with 22 parents of CMC. Reflexive thematic analysis was used to generate themes that described the experiences of PMTS and potential contributing factors in the healthcare setting. Themes were validated by study participants. RESULTS: Parents experienced a spectrum of events and circumstances that impacted PMTS. These corresponded to three major themes: (a) the distinctive context of being the parent of a CMC, (b) interactions with healthcare providers that can hurt or heal and (c) system factors that set the stage for trauma. The consequences of repeated PMTS were a common point of emphasis among all the themes. Parents identified numerous changes that could mitigate PMTS such as acknowledgement of trauma and provision of proactive mental health support. CONCLUSIONS: Our study highlights the issue of PMTS among parents of CMC and presents opportunities to mitigate their traumatic experiences. Supporting the integration of trauma-informed care practices, increasing awareness of PMTS and advocating for parental mental health services could better support parents and families.

The effect domains, measures, and methods reported in pediatric-specialized multidisciplinary outpatient rehabilitation programs: An integrated review.

OBJECTIVES: Specialized pain rehabilitation is recognized as the treatment of choice for youth with pain-related disability. Appropriate outcomes for program evaluation are critical. This study aimed to summarize the effect domains and methods used to evaluate pediatric-specialized outpatient pain rehabilition programs, map them to the PedIMMPACT statement, and highlight future directions. METHODS: An integrated review framework, incorporating stakeholders, was used. Academic Search Complete, CINAHL, ERIC, MEDLINE, PsycINFO, and Google Scholar were searched for studies published in 1999-2021 featuring the treatment effects of specialized outpatient pain rehabilitation on youth with pain-related disability and their parents. Selected studies were critically appraised using the Quality Assessment Tool for Studies of Diverse Design, organized by study characteristics, and analyzed using constant comparison. RESULTS: From the 1951 potentially relevant titles, 37 studies were selected. Twenty-five effects targeted youth and 24 focused on parents, with a maximum of 15 youth and 11 parent effect domains (median = 5 domains per study). Although most studies measured a combination of effect domains and were inclusive of some recommended in the PedIMMPACT statement, no effect was measured consistently across studies. Youth physical functioning and parent emotional functioning were measured most often. Eighty-five instruments were used to assess youth outcomes and 59 for parents, with self-report questionnaires dominating. DISCUSSION: A lack of standardization exists associated with the domains and methods used to evaluate the effects of pediatric-specialized outpatient pain rehabilitation programs, hindering comparisons. Future program evaluations should be founded on their theory, aim, and anticipated outcomes.

Characterizing pain in long-term survivors of childhood cancer.

Many long-term survivors of childhood cancer (LTSCC), individuals at least 5 years post-diagnosis or 2 years post-treatment, experience late- and long-term effects from their treatments, including pain. Yet, pain is poorly understood among LTSCC. The current study aimed to (1a) describe rates and multiple dimensions of pain; (1b) identify patterns of chronic pain; and (2) test correlates of chronic pain in LTSCC. Survivors (n = 140; 48.6% male, Mage = 17.3 years (range = 8-25)) were recruited from across Canada. Between 2017 and 2019, participants completed the Pain Questionnaire, Pain Catastrophizing Scale, Pediatric Quality of Life Inventory, Patient-Reported Outcome Measurement Information System (PROMIS)-Pain Interference, Anxiety, and Depression scales, Child Posttraumatic Stress Scale, the Posttraumatic Stress Disorder Checklist for the DSM-V, and the Cancer Worry Scale. RESULTS: Twenty-six percent of LTSCC reported experiencing chronic pain. Exploratory cluster analysis showed 20% of survivors had moderate to severe chronic pain based on measures of pain intensity and interference. The combination of higher posttraumatic stress symptoms, older current age, more pain catastrophizing, and sex (being female) significantly predicted the presence of chronic pain in logistic regression, χ2 (4, N = 107) = 28.10, p < .001. Higher pain catastrophizing (OR = 1.09; 95% CI = 1.02-1.16), older current age (OR = 1.20; 95% CI = 1.07-1.34), and higher posttraumatic stress (OR = 1.92; 95% CI = 1.01-3.63) were significant predictors of chronic pain. LTSCC should be screened for the presence and magnitude of chronic pain during long-term follow-up visits so appropriate interventions can be offered and implemented. Future research should investigate pain interventions tailored for this population. RELEVANCE: Findings support regular screening for the presence and magnitude of chronic pain in survivors of childhood cancer in long-term follow-up care.

Ensuring Equity and Inclusion in Virtual Care Best Practices for Diverse Populations of Youth with Chronic Pain.

Poor access to care is a top patient-oriented research priority for youth with chronic pain in Canada, and the COVID-19 pandemic has exacerbated these concerns. Our patient-oriented project team engaged with marginalized and racialized youth with chronic pain (Black youth with sickle cell disease, Indigenous youth and youth with complex medical needs) and their families to ensure that best practice recommendations for virtual care are inclusive and equitable. Input provided through virtual round-table discussions improved recommendations for leveraging, implementing and selecting best platforms for virtual care for youth with chronic pain and identified new gaps for future research, practice and policy change.

Pain in long-term survivors of childhood cancer: A systematic review of the current state of knowledge and a call to action from the Children's Oncology Group.

Survivors of childhood cancer may be at risk of experiencing pain, and a systematic review would advance our understanding of pain in this population. The objective of this study was to describe: 1) the prevalence of pain in survivors of childhood cancer, 2) methods of pain measurement, 3) associations between pain and biopsychosocial factors, and 4) recommendations for future research. Data sources for the study were articles published from January 1990 to August 2019 identified in the PubMed, PsycINFO, EMBASE, and Web of Science data bases. Eligible studies included: 1) original research, 2) quantitative assessments of pain, 3) articles published in English, 4) cancers diagnosed between birth and age 21 years, 5) survivors at 5 years from diagnosis and/or at 2 years after therapy completion, and 6) a sample size >20. Seventy-three articles were included in the final review. Risk of bias was considered using the Cochrane risk of bias tool. The quality of evidence was evaluated according to Grading of Recommendations Assessment Development and Evaluation (GRADE) criteria. Common measures of pain were items created by the authors for the purpose of the study (45.2%) or health-related quality-of-life/health status questionnaires (42.5%). Pain was present in from 4.3% to 75% of survivors across studies. Three studies investigated chronic pain according the definition in the International Classification of Diseases. The findings indicated that survivors of childhood cancer are at higher risk of experiencing pain compared with controls. Fatigue was consistently associated with pain, females reported more pain than males, and other factors related to pain will require stronger evidence. Theoretically grounded, multidimensional measurements of pain are absent from the literature.

Father- and Mother-Child Reminiscing About Past Pain and Young Children's Cognitive Skills.

Objective Painful experiences are common, distressing, and salient in childhood. Parent-child reminiscing about past painful experiences is an untapped opportunity to process pain-related distress and, similar to reminiscing about other distressing experiences, promotes children's broader development. Previous research has documented the role of parent-child reminiscing about past pain in children's pain-related cognitions (i.e., memories for pain), but no study to date has examined the association between parent-child reminiscing about past painful experiences and children's broader cognitive skills. Design and Methods One hundred and ten typically developing four-year-old children and one of their parents reminisced about a past painful autobiographical event. Children then completed two tasks from the NIH Toolbox Cognitive Battery, the Flanker Inhibitory Control & Attention Test and the Picture Sequence Memory Test, to measure their executive function and episodic memory, respectively. Results Results indicated that the relation between parental reminiscing style and children's executive function was moderated by child sex, such that less frequent parental use of yes-no repetition questions was associated with boys' but not girls', greater performance on the executive function task. Children displayed greater episodic memory performance when their parents reminisced using more explanations. Conclusions The current study demonstrates the key role of parent-child reminiscing about pain in children's broader development and supports the merging of developmental and pediatric psychology fields. Future longitudinal research should examine the directionality of the relation between parent-child reminiscing about past pain and children's developmental outcomes.

The Socialization of Young Children's Empathy for Pain: The Role of Mother- and Father-Child Reminiscing.

OBJECTIVE: Empathy for pain allows one to recognize, understand, and respond to another person's pain in a prosocial manner. Young children develop empathy for pain later than empathy for other negative emotions (e.g., sadness), which may be due to social learning. How parents reminisce with children about past painful events has been linked to children's pain cognitions (e.g., memory) and broader socioemotional development. The present study examined how parent-child reminiscing about pain may be linked to children's empathic behaviors toward another person's pain. METHODS: One hundred and fourteen 4-year-old children (55% girls) and for each, one parent (51% fathers) completed a structured narrative elicitation task wherein they reminisced about a past painful autobiographical event for the child. Children were then observed responding in a lab-based empathy task wherein they witnessed a confederate pretending to hurt themselves. Children's empathic behaviors and parent-child narratives about past painful events were coded using established coding schemes. RESULTS: Findings revealed that parents who used more neutral emotion language (e.g., How did you feel?) when discussing past painful events had children who exhibited more empathic concern in response to another's pain. Similarly, children who used more explanations when reminiscing about past painful events displayed more empathic concern about another's pain. CONCLUSIONS: Findings highlight a key role of parent-child reminiscing about the past pain in the behavioral expression of empathy for pain in young children.

Children's Pain During IV Induction: A Randomized-Controlled Trial With the MEDi® Robot.

OBJECTIVE: This study examined the impact of a humanoid robot (MEDi®) programmed to teach deep breathing as a coping strategy, on children's pain and fear as primary and secondary outcomes, respectively, during intravenous (IV) line placement. The completion of IV induction was also examined as an exploratory outcome. METHODS: In this randomized controlled, two-armed trial, 137 children (4-12 years) were recruited in Short Stay Surgery at a tertiary pediatric hospital. Patients were randomly assigned to standard care (SC) with Ametop© only (N = 60) or SC and robot-facilitated intervention (N = 59) before induction. Pain and fear before, during, and after IV insertion were rated by patients and observers. RESULTS: No significant differences were found between groups and there were no changes over time for pain or fear (ps > .05). Exploratory analyses show that patients in the MEDi® group were 5.04 times more likely to complete IV induction, compared to SC, Fisher's exact test: X2 (1) = 4.85, p = .04, φc = 0.22, odds ratio = 5.04, 95% CI [1.06, 24.00]. CONCLUSION: This study was the first to examine children's IV induction experience when provided MEDi® support. Reasons for nonsignificance, limitations, and research suggestions were made.

Decreasing Pain and Fear in Medical Procedures with a Pediatric Population (DREAM): A Pilot Randomized Within-Subject Trial.

BACKGROUND: Many children with injuries, including burns and fractures, experience moderate to severe pain during medical procedures. Recent studies claim that nonpharmacologic pain management using virtual reality (VR) could distract children from procedural pain by engaging multiple senses. AIMS: The aims of this pilot randomized clinical trial were to assess the acceptability and feasibility of VR distraction in children with burns or fractures undergoing painful medical procedures, as well as the staff nurses, and assess the preliminary efficacy of VR distraction on pain intensity, pain-related fear, and subsequent recall of both. MATERIALS AND METHOD: A within-subject study design, in which participants served as their own control, was used. A total of 20 children from 7 to 17 years old with an injury were recruited at the surgical-trauma outpatient clinics of the Centre hospitalier universitaire Sainte-Justine (CHU Sainte-Justine). Each participant received both standard and experimental treatments through randomized order. Pain (numerical rating scale) and pain-related fear (Children's Fear Scale) measures were taken before the procedure and after each sequence, followed by a measure of children's (graphic rating scale) and nurses' acceptability of the intervention through their satisfaction level. Recall of pain intensity and pain-related fear were assessed 24 hours after the procedure. Wilcoxon signed-rank tests were used, with a significance level at 0.05. RESULTS: Results showed that VR distraction was an acceptable and feasible intervention for children and nurses of these outpatient clinics. Preliminary effects showed that, compared to standard of care, children participants reported a significant decrease in pain intensity (p = .023) and pain-related fear (p = .011) during VR as well as less recalled pain-related fear (p = .012) at 24 hours after the procedure. No side effects were reported. CONCLUSION: VR is a promising intervention with children undergoing painful procedures because it is immersive and engages multiple senses. It is a low-cost intervention well accepted by children and nursing staff at this clinical site and is easy to implement in daily practice for procedural pain management.

Immersive virtual reality vs. non-immersive distraction for pain management of children during bone pins and sutures removal: A randomized clinical trial protocol.

AIMS: To examine the efficacy of an immersive virtual reality distraction compared with an active non-immersive distraction, such as video games on a tablet, for pain and anxiety management and memory of pain and anxiety in children requiring percutaneous bone pins and/or suture removal procedures. DESIGN: Three-centre randomized clinical trial using a parallel design with two groups: experimental and control. METHODS: Study to take place in the orthopaedic department of three children hospital of the Montreal region starting in 2019. Children, from 7-17 years old, requiring bone pins and/or suture removal procedures will be recruited. The intervention group (N = 94) will receive a virtual reality game (Dreamland), whereas the control group (N = 94) will receive a tablet with video games. The primary outcomes will be both the mean self-reported pain score measured by the Numerical Rating Scale and mean anxiety score, measured by the Child Fear Scale. Recalls of pain and anxiety will be measured 1 week after the procedure using the same scales. We aim to recruit 188 children to achieve a power of 80% with a significance level (alpha) of 5%. DISCUSSION: While multiple pharmacological methods have previously been tested for children, no studies have evaluated the impact of immersive virtual reality distraction for pain and anxiety management in the orthopaedic setting. IMPACT: Improved pain management can be achieved using virtual reality during medical procedures for children. This method is innovative, non-pharmacological, adapted to the hospital setting, and user-friendly. TRIAL REGISTRATION: NCT03680625, registered on clinicaltrials.gov.

Age-related differences in resting state functional connectivity in pediatric migraine.

BACKGROUND: Migraine affects roughly 10% of youth aged 5-15 years, however the underlying mechanisms of migraine in youth are poorly understood. Multiple structural and functional alterations have been shown in the brains of adult migraine sufferers. This study aims to investigate the effects of migraine on resting-state functional connectivity during the period of transition from childhood to adolescence, a critical period of brain development and the time when rates of pediatric chronic pain spikes. METHODS: Using independent component analysis, we compared resting state network spatial maps and power spectra between youth with migraine aged 7-15 and age-matched controls. Statistical comparisons were conducted using a MANCOVA analysis. RESULTS: We show (1) group by age interaction effects on connectivity in the visual and salience networks, group by sex interaction effects on connectivity in the default mode network and group by pubertal status interaction effects on connectivity in visual and frontal parietal networks, and (2) relationships between connectivity in the visual networks and the migraine cycle, and age by cycle interaction effects on connectivity in the visual, default mode and sensorimotor networks. CONCLUSIONS: We demonstrate that brain alterations begin early in youth with migraine and are modulated by development. This highlights the need for further study into the neural mechanisms of migraine in youth specifically, to aid in the development of more effective treatments.

The Development of Adolescent Chronic Pain following Traumatic Brain Injury and Surgery: The Role of Diet and Early Life Stress.

Pain is evolutionarily necessary for survival in that it reduces tissue damage by signaling the body to respond to a harmful stimulus. However, in many circumstances, acute pain becomes chronic, and this is often dysfunctional. Adolescent chronic pain is a growing epidemic with an unknown etiology and limited effective treatment options. Given that the relationship between acute pain and chronic pain is not straightforward, there is a need to better understand the factors that contribute to the chronification of pain. Since early life factors are critical to a variety of outcomes in the developmental and adolescent periods, they pose promise as potential mechanisms that may underlie the transition from acute to chronic pain. This review examines two early life factors: poor diet and adverse childhood experiences (ACEs); they may increase susceptibility to the development of chronic pain following surgical procedures or traumatic brain injury (TBI). Beyond their high prevalence, surgical procedures and TBI are ideal models to prospectively understand mechanisms underlying the transition from acute to chronic pain. Common themes that emerged from the examination of poor diet and ACEs as mechanisms underlying this transition included: prolonged inflammation and microglia activation leading to sensitization of the pain system, and stress-induced alterations to hypothalamic-pituitary-adrenal axis function, where cortisol is likely playing a role in the development of chronic pain. These areas provide promising targets for interventions, the development of diagnostic biomarkers, and suggest that biological treatment strategies should focus on regulating the neuroinflammatory and stress responses in an effort to modulate and prevent the development of chronic pain.